We propose to extend our epidemiological study of basal cell (BCC) and squamous cell (SCC) skin cancer to: (1) measure recent changes in the incidence of these tumors in a geographically-defined USA population, (2) define the dose-response relationship between inorganic arsenic exposure and risk of BCC and SCC, and (3) assess the effects of use of glucocorticoids in the etiology of these malignancies. In the previous grant period, we successfully established a collaborative network of over 50 dermatologists and pathology laboratories in New Hampshire and bordering states, and developed procedures for identifying cases and abstracting data on BCC and SCC occurrences. Our preliminary results show that the incidence of BCC and SCC have markedly increased since a comparably conducted survey conducted in NH 15 years earlier. We now propose to continue surveillance of these malignancies to permit assessment of age-, sex- and site-specific trends in the incidence rates of BCC and SCC over a total span of twenty years (1979 to 2000). We have also established a case-control study of BCC and SCC based on the incidence surveillance system. In addition to clarifying the risk of BCC and SCC due to previously hypothesized factors (e.g., sun exposure), our preliminary data indicate that risk may be associated with toenail concentrations of arsenic and with use of glucocorticoid medications. We propose to confirm and extend these findings through a continued and expanded case-control study. We will enroll an additional 600 SCC and 600 BCC cases identified in the incidence survey, and 600 controls randomly selected from population lists maintained by the NH Department of Motor Vehicles (for those less than 65 years) and the Health Care Financing Administration (for those greater than or equal to 65 years). We will conduct in-person interviews to assess medication use and will obtain toenail samples for arsenic determinations using Neutron Activation Analysis. We also will test household water samples for arsenic using a High Resolution Inductively Coupled Plasma Mass Spectrometer (ICP-MS), and will bank WBC DNA on all cases and controls. This project will provide long term data on BCC and SCC incidence in the USA, and it is one of the few population-based studies worldwide for risk factor assessment of these common, and potentially preventable tumors.